| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Total, LDL, and HDL cholesterol decrease with age in older men and women. The Rancho Bernardo Study 1984-1994 Ferrara, A., E. Barrett-Connor, et al. (1997), Circulation 96(1): 37-43. Abstract: BACKGROUND: The purpose of the present study was to study the effects of age, weight change, and covariates on lipid and lipoprotein levels cross-sectionally and prospectively in an elderly population. METHODS AND RESULTS: A community-based sample of 1041 men and 1303 women aged 50 to 93 years was studied cross-sectionally in 1984 to 1987, with follow-up of 372 men and 545 women 8 years later. In the cross-sectional study, levels of total cholesterol (TC) and LDL cholesterol (LDL-C) decreased and levels of HDL cholesterol (HDLC) increased with age in men (all P <.001) but not in women. In the prospective study, TC, LDL-C, and HDL-C levels all decreased in both men and women, in all age groups (50 to 64 years, 65 to 74 years, and > or = 75 years) and in all weight change groups (> 2.5-kg loss, change within 2.5 kg, and > 2.5-kg gain) and in all waist girth change groups, for an overall decrement of approximately 1% per year. In multiple linear regression models, change in weight was the most important independent and consistent predictor of changes in TC, LDL-C, and HDL-C. Similar results were obtained in analyses excluding subjects taking lipid-lowering drugs or estrogen and in analyses adjusted for changes in cigarette smoking, alcohol intake, physical activity, medication use, and incident myocardial infarction, cancer, or diabetes. CONCLUSIONS: Cross-sectional decrements in TC and LDL-C with age in men are not explained by survivor bias because they are also observed prospectively. Although weight change was the most important explanatory variable, TC, LDL-C, and HDL-C levels also decreased in those who lost or gained weight. Age was not an independent predictor of change. Other prospective studies are recommended to better define the causes and consequences of cholesterol and lipoprotein changes in old age. |
| Toward a more balanced cholesterol policy Hulley, S. B., T. B. Newman, et al. (1994), Circulation 90(5): 2570-2; author reply 2573-7. |
| Toward the prevention of coronary heart disease: screening of children and adolescents for high blood cholesterol Reece, S. M. (1995), Nurse Pract 20(2): 22, 24-6, 31 passim. Abstract: Coronary heart disease (CHD) remains the number one killer in the United States. This article summarizes the recommendations for cholesterol screening of children and adolescents by the American Academy of Pediatrics and the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Screening of children and adolescents is selective, and the determination to screen is based on past medical, family health, and health behavior histories. Children or adolescents with a family history of peripheral vascular disease or coronary artery disease in primary relatives under 55 years of age, or parents with high blood cholesterol levels, are considered to be at risk for high blood cholesterol and in need of screening. Children or adolescents who are obese, inactive, have hypertension or diabetes, or who smoke are also considered to be at risk. A universal approach to the prevention of CHD through diet and lifestyle is also described. |
| Toxicity and therapeutic efficacy of amphotericin B delivered through cholesterol hemisuccinate vesicles in the treatment of experimental murine aspergillosis Saxena, S., J. A. Khan, et al. (1998), J Antimicrob Chemother 42(5): 635-42. Abstract: We have studied the toxicity and therapeutic efficacy of amphotericin B in cholesterol hemisuccinate vesicles (ABCV) in the treatment of invasive aspergillosis in Balb/c mice. The toxicity of amphotericin B was significantly reduced when delivered through cholesterol hemisuccinate vesicles as compared to deoxycholate suspension (AmB(DOC)) as evidenced by reduced nephrotoxicity in Balb/c mice, lower in-vitro toxicity to erythrocytes and higher maximum tolerated dose. The latter increased from 2 mg/kg wt for AmB(DOC) to 17 mg/kg wt for ABCV. The vesicles had a mean diameter of 252 nm. In order to evaluate the therapeutic efficacy of ABCV, Aspergillus fumigatus-infected mice were treated with ABCV 2, 4, 8 or 12 mg/kg or AmB(DOC) 1 mg/kg wt. The antifungal activity was highly dependent on the dosage of ABCV on the basis of survival of treated mice and cfu in lung, liver, spleen and kidney. This study found that ABCV had dose-dependent antifungal activity and therapeutic efficacy in the treatment of invasive aspergillosis in Balb/c mice. |
| Toxicity of cholesterol oxidation products to Caco-2 and HepG2 cells: modulatory effects of alpha- and gamma-tocopherol O'Sullivan, A. J., Y. C. O'Callaghan, et al. (2003), J Appl Toxicol 23(3): 191-7. Abstract: Cholesterol can be oxidized to form a variety of cholesterol oxidation products also known as oxysterols. The aims of the present study were to compare the cytotoxic effects of four oxysterols, namely 25-hydroxycholesterol (25-OHC), 7beta-hydroxycholesterol (7beta-OHC), cholesterol-5beta,6beta-epoxide (beta-epox) and cholesterol-5alpha,6alpha-epoxide (alpha-epox), in two human cell culture models. Further, the ability of 10 and 100 micro m alpha- and gamma-tocopherol (alpha-TOC and gamma-TOC, respectively) to protect against oxysterol-induced cytotoxicity was also assessed. Human colonic adenocarcinoma Caco-2 and human hepatoma HepG2 cells were supplemented with increasing concentrations of 25-OHC, 7beta-OHC, beta-epox and alpha-epox (0-25 micro g ml(-1)) for 24, 48 or 96 h. Following 24-h and 48-h exposure, test media were replaced with normal growth media and the cells were maintained for 72 and 48 h, respectively. The 96-h exposure represented a constant challenge to the cells. Cytotoxicity was assessed using the neutral red uptake assay. The concentration of compound that inhibited cell viability by 50% (ic(50) value) was calculated. All four oxysterols investigated induced the greatest cytotoxic effects following 96 h of exposure. 25-Hydroxycholesterol exhibited the greatest cytotoxicity in both cell lines. Both beta-epox and alpha-epox were more toxic to HepG2 cells than to Caco-2 cells after the 48-h exposure. Pretreatment of cells with either alpha- or gamma-TOC did not protect against oxysterol-induced cytotoxicity. The caco-2 cells treated with the high concentration (100 micro m) of gamma-TOC were found to be more susceptible to oxysterol-induced toxicity under the conditions employed in this study. |
| Toxicity of cholesterol oxides on cultured neuroretinal cells Chang, J. Y. and L. Z. Liu (1998), Curr Eye Res 17(1): 95-103. Abstract: PURPOSE: By using nerve growth factor-differentiated PC12 cells as a model for sympathetic neurons, we have recently shown that cholesterol oxides are toxic to cells of neural origin. Since lipid metabolism is known to be involved in some pathological conditions associated with the visual system, we sought to extend this line of research by studying the potential cytotoxicity of cholesterol oxides on primary cultures derived from neuroretinas. METHODS: Dissociated cultures derived from neuroretinas of 1-day-old Sprague-Dawley rats were used in this series of studies. Immunohistochemical staining was used to identify neuronal and glial cell types in these cultures. MTT assay was used to determine the cytotoxicity of cholesterol oxides, including 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH- and 25-OH-cholesterol. RESULTS: Among the cholesterol oxides tested, 7-beta-OH- and 7-keto-cholesterol were the most effective in causing cell death, such that 20 micrograms/ml (50 microM) of these agents killed approximately 80% of cells in 3 days. A time-dependent experiment indicated that 10 micrograms/ml of 7-beta-cholesterol was able to kill 50% of cells in approximately 5 h. A number of pharmacological agents were tested for their ability to prevent cell death induced by cholesterol oxides. Among them, vitamin E and methyl-beta-cyclodextrin were able to prevent cholesterol oxide-induced cell death in a dose-dependent manner. CONCLUSIONS: These results suggest that, in addition to causing pathological changes in cells directly involved in atherosclerosis, cholesterol oxides may be toxic to cells derived from neuroretinas. |
| Toxicity of oxygenated cholesterol derivatives toward cultured human umbilical vein endothelial cells Pettersen, K. S., K. M. Boberg, et al. (1991), Arterioscler Thromb 11(2): 423-8. Abstract: Human umbilical vein endothelial cells were cultured in the presence of several oxygenated cholesterol derivatives that are known to affect the viability of other cell lines. 5-Cholestene-3 beta,7 beta-diol (7 beta-hydroxycholesterol) caused a time- and concentration-dependent perturbation of the endothelial cells. Exposure to 50 mumol/l of this compound for 18 hours resulted in marked contraction of the cells, followed by increasing cell detachment from the substrate and Trypan Blue uptake in detached cells. Concomitantly release of lactate dehydrogenase from the cells reached about 80% at 24 hours. The release of tissue plasminogen activator and tissue plasminogen activator inhibitor-1 antigens decreased at a concentration of 7 beta-hydroxycholesterol lower than that required for reducing general protein synthesis. 7 beta-Hydroxycholesterol at 50 mumol/l first increased the release and then (at 100 mumol/l) inhibited the synthesis of von Willebrand factor. Incubation with 100 mumol/l of 5-cholestene-3 beta, 7 alpha,22(R)-triol (7 alpha,22-dihydroxycholesterol)e and the isomeric 5-cholestene-3 beta, 7 beta, 22(R)-triol (7 beta, 22-dihydroxycholesterol) caused formation of intercellular gaps and some detachment of the cells after 24 hours. Cell injury was slightly more pronounced for the 7 alpha, 22-dihydroxycholesterol than for the 7 beta-isomer. Incubations with cholesterol under the same conditions gave no sign of cell injury. |
| Toxicologic effects of a novel acyl-CoA:cholesterol acyltransferase inhibitor in cynomolgus monkeys Reindel, J. F., M. A. Dominick, et al. (1994), Toxicol Pathol 22(5): 510-8. Abstract: PD 132301-2, an acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, was administered orally to cynomolgus monkeys for 2 wk at doses of 25, 50, 100, and 200 mg/kg to assess potential subacute toxicity. Sporadic episodes of soft feces and diarrhea increased in incidence from 100 to 200 mg/kg. Histopathologic alterations in adrenocortical cells of treated monkeys consisted of a dose-related decrease in cytoplasmic fine vacuolation and an increase in cytoplasmic eosinophilia most conspicuous in the zona fasciculata and reticularis. At 50, 100, and 200 mg/kg, a narrow discontinuous zone of cytotoxic cortical cell degeneration occurred in the outer zona fasciculata. Decreased fine vacuolation of cortical cells correlated ultrastructurally with reduced size and number of intracellular lipid vacuoles and biochemically with a dose-related decrease in adrenal total cholesterol (from 56 to 13% of control) and cholesteryl ester (from 51 to 3% of control) concentrations. Other ultrastructural changes noted in zona fasciculata cortical cells at all doses were an apparent increase in both smooth endoplasmic reticulum and variably sized autophagic vacuoles. Ovarian corpora lutea in some females at all doses had increased coarse vacuolation of luteal cells, foci of cellular degeneration, increased numbers of cholesterol clefts, and slight infiltrates of mononuclear cells. Sebaceous glands were atrophic in all treated monkeys due largely to a reduction in size and number of differentiated foam cells. Sebaceous gland reserve cells were hypertrophic and hyperplastic. Toxicity data from this study indicated that PD 132301-2 at 25-200 mg/kg targeted cholesterol-rich cells of the adrenals, ovaries, and skin adnexa. |
| Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated endocytosis for cholesterol acquisition Coppens, I., A. P. Sinai, et al. (2000), J Cell Biol 149(1): 167-80. Abstract: The obligate intracellular protozoan Toxoplasma gondii resides within a specialized parasitophorous vacuole (PV), isolated from host vesicular traffic. In this study, the origin of parasite cholesterol was investigated. T. gondii cannot synthesize sterols via the mevalonate pathway. Host cholesterol biosynthesis remains unchanged after infection and a blockade in host de novo sterol biosynthesis does not affect parasite growth. However, simultaneous limitation of exogenous and endogenous sources of cholesterol from the host cell strongly reduces parasite replication and parasite growth is stimulated by exogenously supplied cholesterol. Intracellular parasites acquire host cholesterol that is endocytosed by the low-density lipoprotein (LDL) pathway, a process that is specifically increased in infected cells. Interference with LDL endocytosis, with lysosomal degradation of LDL, or with cholesterol translocation from lysosomes blocks cholesterol delivery to the PV and significantly reduces parasite replication. Similarly, incubation of T. gondii in mutant cells defective in mobilization of cholesterol from lysosomes leads to a decrease of parasite cholesterol content and proliferation. This cholesterol trafficking to the PV is independent of the pathways involving the host Golgi or endoplasmic reticulum. Despite being segregated from the endocytic machinery of the host cell, the T. gondii vacuole actively accumulates LDL-derived cholesterol that has transited through host lysosomes. |
| Toxoplasma gondii Rab5 enhances cholesterol acquisition from host cells Robibaro, B., T. T. Stedman, et al. (2002), Cell Microbiol 4(3): 139-52. Abstract: The role of endocytosis in nutrient uptake by Toxoplasma gondii is unknown. To explore this issue, we characterized an endosomal compartment by identifying a T. gondii Rab5 homologue, a molecular marker for early endosomes in eukaryotic cells. The deduced amino acid sequence of the T. gondii Rab5 gene encodes a protein of 240 amino acids, which we termed TgRab51. TgRab51 was epitope-tagged at the N-terminus, expressed in the parasite, and localized by immunofluorescence and immunoelectron microscopy to tubulovesicular structures anterior to the parasite nucleus and adjacent to, but distinct from the Golgi. By immunofluorescence analysis, TgRab51wt-HA staining partially overlapped with Golgi/TGN markers, but not with the T. gondii secretory organelles. A dominant positive mutant, TgRab51Q103L-HA, enhanced uptake of exogenous cholesterol analogues in intracellular parasites, augmented formation of lipid droplets and accelerated parasite growth. Brefeldin A disrupted the TgRab51 compartment, and altered the distribution of fluorescent exogenous cholesterol in cells expressing TgRab51Q103L-HA. These results suggest that TgRab51 facilitates sterol uptake, possibly through a Golgi-dependent pathway. |
| Tracking cell cholesterol with cholesterol oxidase Lange, Y. (1992), J Lipid Res 33(3): 315-21. |
| Tracking of serum cholesterol and lipoprotein levels from the first year of life Kallio, M. J., L. Salmenpera, et al. (1993), Pediatrics 91(5): 949-54. Abstract: OBJECTIVE. To examine the development of tracking of serum cholesterol concentration from birth to childhood. DESIGN. In a longitudinal study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193); at 2 (n = 192), 4 (n = 192), 6 (n = 190), 7.5 (n = 118), 9 (n = 188), and 12 months (n = 196); and at 5 years of age (n = 162). Concentrations of cholesterol--very-low-density lipoprotein, low-density lipoprotein, high-density lipoprotein-2 (HDL2), and HDL3--were determined at 2, 6, 9, and 12 months (n = 36) and at 5 years (n = 162). RESULTS. The correlation coefficients of total cholesterol levels during the first year of life with the level at 5 years of age were as follows: at birth.04, at 2 months.36 (P <.001), at 4 months.26 (P <.001), at 6 months.28 (P <.001), at 7.5 months.25 (P <.001), at 9 months.35 (P <.001), and at 12 months.48 (P <.001). The correlation for exclusively breast-fed children between 6 months and 5 years of age was r =.37, P <.001, while that for children receiving partially breast milk, formula, or solid foods was r =.12, P = not significant (NS), and between 9 months and 5 years r =.38, P <.01, and r =.28, P <.05, respectively. The correlation coefficients of the lipoprotein levels between ages 12 months and 5 years were as follows: low-density lipoprotein cholesterol.58 (P <.001), total HDL cholesterol.30 (P <.05), HDL2 cholesterol.34 (P <.05), HDL3 cholesterol.17 (P = NS), very-low-density lipoprotein cholesterol.24 (P = NS), total triglyceride.37 (P <.05), and triglyceride-very-low-density lipoprotein.37 (P <.05). Of the children whose total serum cholesterol level was above the 90th percentile at birth, or at 2, 4, 6, 7.5, 9, or 12 months, 6%, 35%, 29%, 30%, 31%, 33%, and 45%, respectively, were above the 90th percentile at 5 years of age. In retrospect, 45% of the children whose serum cholesterol level was above the 90th percentile at 5 years were above the 90th percentile at the age of 12 months and 80% were in the highest quartile. CONCLUSIONS. The results indicate that tracking of serum cholesterol concentration during the first year of life is stronger when examining children who are receiving a relatively homogenous diet, such as exclusive breast-feeding, and weaker as children are weaned to formula and solid foods. After the weaning process is completed, children's relative serum cholesterol levels have become established and the tracking of serum cholesterol is of the same magnitude as for older children and adolescents. |
| Tracking of serum cholesterol levels in a multiracial sample of preschool children Freedman, D. S., T. Byers, et al. (1992), Pediatrics 90(1 Pt 1): 80-6. Abstract: The relation of an initial measurement of serum total cholesterol to subsequent levels over a (mean) 13-month interval was examined in a multiracial (white, Hispanic, American Indian, and black) sample of 1680 one- to four-year-olds. Although the relation of the initial level to the final measurement (r =.54) did not vary by race, sex, relative weight, or changes in relative weight, the association increased with age at the time of the initial measurement (eg, r =.64 among 4-year-olds). Based on the initial and final total cholesterol determinations, the within-person standard deviation was 21 mg/dL and the coefficient of variation was 13%. Although the final total cholesterol level was within 5 mg/dL of the initial level for 18% of the children, the two determinations differed by greater than or equal to 25 mg/dL for about 35% of the children and by greater than or equal to 50 mg/dL for about 8%. Of the 149 children who had an initial cholesterol level greater than or equal to 200 mg/dL, 34% (about five times the expected number) had a follow-up level that was similarly elevated whereas 25% had a subsequent measurement below 170 mg/dL. The results indicate that although an initial cholesterol level in early life is moderately predictive of subsequent levels, it may be difficult to interpret a single total cholesterol determination because of substantial within-person variability. |
| Tracking of serum HDL-cholesterol and other lipids in children and adolescents: the Cardiovascular Risk in Young Finns Study Porkka, K. V., J. S. Viikari, et al. (1991), Prev Med 20(6): 713-24. Abstract: BACKGROUND. We have studied the tracking (i.e., the correlation between subsequent measurements) of serum lipids in a cohort of 2,236 children and adolescents (ages initially 3-18 years). METHODS. Determinations of the serum variables were made 3 and 6 years apart. Six-year tracking values (Spearman's r) were 0.63, 0.66, 0.58, and 0.36 for serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, respectively. Boys were found to track better than girls. Subjects who remained persistently in the highest (total cholesterol, low-density lipoprotein cholesterol, and triglycerides) or lowest (high-density lipoprotein cholesterol and high-density lipoprotein ratio) quintile tended to become obese and smoked cigarettes more frequently than the others. CONCLUSION. The tracking of high-density lipoprotein cholesterol was higher than in previous studies, but differences in methodology may account for this. We conclude that total cholesterol and low-density as well as high-density lipoprotein cholesterol measurements in childhood and adolescence are predictive of adult values. |
| Tracking of serum lipoprotein (a) concentration and its contribution to serum cholesterol values in children from 7 to 36 months of age in the STRIP Baby Study. Special Turku Coronary Risk Factor Intervention Project for Babies Routi, T., T. Ronnemaa, et al. (1997), Ann Med 29(6): 541-7. Abstract: We investigated the tracking phenomenon of serum lipoprotein (a) concentrations and assessed the impact of serum concentration of lipoprotein (a) cholesterol on total cholesterol concentrations in children from 7 to 36 months of age. Serum samples for lipoprotein (a) and cholesterol determinations at 7, 13, 24 and 36 months were prospectively obtained from 430 children. Serum lipoprotein (a) was determined using immunoradiometric assay. A strong correlation was observed between lipoprotein (a) concentrations at 7 and 36 months of age (r = 0.88, P < 0.001). Seventy-eight per cent to 86% of the children in the lowest and highest lipoprotein (a) quintiles at 13 months remained in the respective quintiles at 36 months. The average contribution of lipoprotein (a) cholesterol to total cholesterol varied from 0.5% to 3.2% (individual variation 0.13-32.39%) depending on the type of milk received and the age of the children. At 7 months the contribution was 0.44% in breast-fed and 0.93% in formula-fed infants (P < 0.0001). The tracking phenomenon of serum lipoprotein (a) concentrations is strong already in early childhood. The contribution of lipoprotein (a) cholesterol to serum total cholesterol concentration should be taken into account when the changes in serum cholesterol levels are interpreted in the first year of life. |
| Tracking of serum total cholesterol during childhood: an 8-year follow-up population-based family study in eastern Finland Fuentes, R. M., I. L. Notkola, et al. (2003), Acta Paediatr 92(4): 420-4. Abstract: AIM: To investigate the tracking of serum total cholesterol (TC) during childhood. METHODS: All children born during 1981-1982 in a rural community of eastern Finland were followed at 6 mo, 7 y and 15 y of age. The full follow-up period was completed by 138 out of 205 children, of whom 82 (33 girls) had TC measured at 7 y and 15 y of age (-7 y, -15 y). The main outcome measurement was TC (mmol/L). RESULTS: TC-7 y was significantly associated with TC-15 y (r = 0.655; p-value < 0.001). This correlation did not change significantly after accounting for confounders. Children in the highest tertile of TC-7 y had a significantly higher risk of being in the highest tertile of TC-15 y compared with children in other tertiles of TC-7 y (relative risk = 6.4 (2.9-13.9)). TC-15 y was predicted positively by TC-7 y (linear regression beta = 0.63; p-value < 0.001) and parental high TC (TC > or = 5.0 mmol/L in at least one parent) (beta = 0.58; p-value = 0.030). Birthweight had no significant association with TC during childhood. CONCLUSION: The study confirmed the tracking of TC during childhood. The identification of children at risk of developing high TC during adolescence should take into consideration the child's previous TC values during childhood and parental TC status. |
| Trafficking defects in endogenously synthesized cholesterol in fibroblasts, macrophages, hepatocytes, and glial cells from Niemann-Pick type C1 mice Reid, P. C., S. Sugii, et al. (2003), J Lipid Res 44(5): 1010-9. Abstract: Niemann-Pick type C1 disease (NPC1) is an inherited neurovisceral lipid storage disorder, hallmarked by the intracellular accumulation of unesterified cholesterol and glycolipids in endocytic organelles. Cells acquire cholesterol through exogenous uptake and endogenous biosynthesis. NPC1 participation in the trafficking of LDL-derived cholesterol has been well studied; however, its role in the trafficking of endogenously synthesized cholesterol (endoCHOL) has received much less attention. Previously, using mutant Chinese hamster ovary cells, we showed that endoCHOL moves from the endoplasmic reticulum (ER) to the plasma membrane (PM) independent of NPC1. After arriving at the PM, it moves between the PM and internal compartments. The movement of endoCHOL from internal membranes back to the PM and the ER for esterification was shown to be defective in NPC1 cells. To test the generality of these findings, we have examined the trafficking of endoCHOL in four different physiologically relevant cell types isolated from wild-type, heterozygous, and homozygous BALB/c NPC1NIH mice. The results show that all NPC1 homozygous cell types (embryonic fibroblasts, peritoneal macrophages, hepatocytes, and cerebellar glial cells) exhibit partial trafficking defects, with macrophages and glial cells most prominently affected. Our findings suggest that endoCHOL may contribute significantly to the overall cholesterol accumulation observed in selective tissues affected by Niemann-Pick type C disease. |
| Trafficking of cholesterol from cell bodies to distal axons in Niemann Pick C1-deficient neurons Karten, B., D. E. Vance, et al. (2003), J Biol Chem 278(6): 4168-75. Abstract: Niemann Pick type C (NPC) disease is a progressive neurodegenerative disorder. In cells lacking functional NPC1 protein, endocytosed cholesterol accumulates in late endosomes/lysosomes. We utilized primary neuronal cultures in which cell bodies and distal axons reside in separate compartments to investigate the requirement of NPC1 protein for transport of cholesterol from cell bodies to distal axons. We have recently observed that in NPC1-deficient neurons compared with wild-type neurons, cholesterol accumulates in cell bodies but is reduced in distal axons (Karten, B., Vance, D. E., Campenot, R. B., and Vance, J. E. (2002) J. Neurochem. 83, 1154-1163). We now show that NPC1 protein is expressed in both cell bodies and distal axons. In NPC1-deficient neurons, cholesterol delivered to cell bodies from low density lipoproteins (LDLs), high density lipoproteins, or cyclodextrin complexes was transported into axons in normal amounts, whereas transport of endogenously synthesized cholesterol was impaired. Inhibition of cholesterol synthesis with pravastatin in wild-type and NPC1-deficient neurons reduced axonal growth. However, LDLs restored a normal rate of growth to wild-type but not NPC1-deficient neurons treated with pravastatin. Thus, although LDL cholesterol is transported into axons of NPC1-deficient neurons, this source of cholesterol does not sustain normal axonal growth. Over the lifespan of NPC1-deficient neurons, these defects in cholesterol transport might be responsible for the observed altered distribution of cholesterol between cell bodies and axons and, consequently, might contribute to the neurological dysfunction in NPC disease. |
| Training health professionals and lay volunteers to deliver cholesterol screening and education programs Linnan, L. A., K. M. Gans, et al. (1990), Public Health Rep 105(6): 589-98. Abstract: The National Heart, Lung, and Blood Institute of the National Institutes of Health launched the National Cholesterol Education Program (NCEP) in 1985. With the goal of reducing the prevalence of elevated blood cholesterol in the United States, the NCEP aims to raise awareness and understanding in both health professionals and the general public of high blood cholesterol levels as a risk factor for coronary heart disease. Public interest in blood cholesterol measurement has created an enormous market for cholesterol screening and education programs. The importance of quality screening and educational services was recognized by the NCEP, which has urged the training of all personnel involved in public cholesterol screenings. This paper presents models for training lay volunteers and health professionals to deliver quality public screening programs for high blood cholesterol that are consistent with NCEP recommendations. Blood cholesterol screening, counseling, and referral (SCORE) programs are key intervention strategies of the Pawtucket Heart Health Program (PHHP), a cardiovascular disease prevention research program in Pawtucket, RI. This paper describes the PHHP volunteer training and certification program for cholesterol SCOREs and the demographics of screening volunteers. With the goal of improving the quality of cholesterol screening and education programs nationally, the Cholesterol Training Center (CTC) was established in 1988. Using models established by PHHP, the center developed training workshops to help health professionals initiate, update, expand, or enhance training for cholesterol screening and education programs. CTC training protocols and the characteristics of workshop participants are described, and the workshops' effects on participants' knowledge and self-sufficiency are discussed. |
| Tranilast suppresses the vascular intimal hyperplasia after balloon injury in rabbits fed on a high-cholesterol diet Fukuyama, J., K. Ichikawa, et al. (1996), Eur J Pharmacol 318(2-3): 327-32. Abstract: Intimal hyperplasia is a serious problem after percutaneous transluminal coronary angioplasty. In this study, we assessed the effect of tranilast on vascular intimal hyperplasia after balloon injury in rabbits fed on a high-cholesterol diet. In this animal model, intimal hyperplasia more severe than that in rabbits fed on a normal diet was observed. In addition, medial thickening and lipid deposits in both media and intima were also noted. These findings indicate that balloon injury caused intimal and medial hyperplasia and that this hyperplasia was accelerated by the high cholesterol load. Tranilast (300 mg/kg) significantly decreased the intimal area, medial area, and stenosis ratio, and increased the luminal/total area ratio, in the cholesterol-fed rabbits. These results suggest that tranilast may be useful for prevention of restenosis after percutaneous transluminal coronary angioplasty of patients, including those with a clinical risk of hypercholesterolemia. |